Objective To investigate the intervention effects of fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) diets on the behaviors and gastrointestinal dysfunction of rat model of autism spectrum disorder (ASD) induced by maternal immune activation (MIA), in order to provide a new approach for ASD intervention therapy based on intestinal function improvement. Methods Twenty-four Wistar pregnant rats were randomly divided into a MIA model group and a control (NS) group. On gestational day 15 (GD15), pregnant rats in the MIA group were intraperitoneally injected with 10mg/kg of Poly(I∶C), while those in the control group were injected with the same volume of 0.9% sterile saline. Three hours later, blood was collected from the live heart, and the levels of interleukin-6 (IL-6), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) were measured by ELISA. Male offspring were randomly divided into four groups: model group-regular diet (MIA-Con), model group-prebiotic diet (MIA-Fos+Gos), control group-regular diet (NS-Con), and control group-prebiotic diet (NS-Fos+Gos). Rats in the MIA-Fos+Gos and NS-Fos+Gos groups were fed with customized FOS+GOS diets starting from weaning at 3 weeks of age for 5 consecutive weeks. After the intervention, behavioral tests including the open field test, three-chamber social interaction test, marble burying test, and grooming test, as well as gastrointestinal function assessments such as fecal water content and small intestinal transit rate, were conducted. Results Compared with the NS group, the levels of IL-6, IFN-γ, and TNF-α in the serum of pregnant rats in the MIA group significantly increased (t=2.390, 2.525, 2.305, P<0.05), indicating an immune-activated state. Compared with the NS-Con group, rats in the MIA-Con group exhibited significantly decreased total movement distance and number of crossed grid lines in the center zone during the open field test, reduced social ability index and social preference index, increased number of buried marbles, and prolonged grooming time(P<0.05). Additionally, the fecal water content and small intestinal transit rate increased in the MIA-Con group (P<0.05). After the intervention of FOS+GOS diet, compared with the MIA-Con group, rats in the MIA-Fos+Gos group showed that the total movement distance in the open field test of increased, the social ability index and social preference index improved, the number of buried marbles decreased, and the grooming time shortened (P<0.05). Furthermore, the fecal water content and small intestinal propulsion rate decreased in the MIA-Fos+Gos group (P<0.05). Conclusion The FOS+GOS diet could attenuate social deficits, anxiety and stereotypical behaviors, and gastrointestinal dysfunction of male offspring which induced by MIA.
Key words
fructo-oligosaccharides and galacto-oligosaccharides /
maternal immune activation /
autism-like behaviors /
gastrointestinal function
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